Caveolin and MAP kinase interaction in angiotensin II preconditioning of the myocardium

Abstract

Angiotensin II (Ang II) has been found to exert preconditioning (PC)-like effect in mammalian hearts. The present investigation reported for the first time a unique mitogen activated protein (MAP) kinase signalling in Ang II PC of the heart involving lipid rafts, which generated a survival signal by differentially associating MAP kinases with caveolin. A group of rat hearts was treated with Ang II in the absence or presence of NADPH oxidase inhibitor, apocynin or a cell permeable reactive oxygen species (ROS) scavenger, N-acetyl-cysteine (NAC). Ang II pre-treatment improved post-ischaemic ventricular recovery, myocardial infraction and decreased the number of cardiomyocyte apoptosis indicating PC effect of Ang II. Both apocynin and NAC abolished the PC ability of Ang II. In Ang II treated heart, there was a decreased association of p38MAPKbeta & extracellular-signal regulated kinase (ERK) 1/ 2 (anti-death signalling component) with caveolin while there was an increased association of p38MAPKalpha & Jun N-terminal kinase (JNK) (death signalling component) indicating reduced amount of death signal components and increased amount of anti-death signalling components being available to the Ang II treated heart to generate a survival signal, which was reversed with NAC or apocynin. The survival signal was also demonstrated by increased phosphorylation of serine/threonine-protein kinase B (AKT) and enhanced induction of expression of Bcl-2 during Ang II PC and its reversal with NAC & apocynin treated heart.

1

Effect of Ang II, NAC & apocynin on the infract size of the heart and cardiomyocyte apoptosis. A:Infract size, B:car-diacmyocyte apoptosis.The results are mean ± SEM of six animal per group *P < 0.05 versus I/R, †P < 0.05 versus Ang II.

2

Differential interaction of p38MAPK, JNK, ERK 1/2 and eNOS with caveolin-1 and caveolin-3 during ischaemia reperfusion, Ang II precondition in presence or absence of NAC or apocynin.The results are mean ± SEM of six animal per group *P < 0.05 versus I/R, †P < 0.05 versus Ang II.

3

Distribution of p38MAPKα, p38MAPKβ, ERK and JNK in different fraction of the Ang II preconditioned heart.

4

Effect of Ang II, NAC & apocyanin on the induction of expression of Bcl-2, AKT and Phospho-AKT. The results are mean ± SEM of six animal per group *P < 0.05 versus I/R, †P < 0.05 versus Ang II.